Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.

Chaihu Guizhi Ganjiangtang （CGG）is a classic prescription in the Treatise on Cold Damage，which has the effects of clearing and relieving stagnation heat in Shaoyang，warming and dissolving water drink，and relieving the pivot mechanism. It is a classic prescription for treating spleen deficiency and liver depression and stopping internal stagnation caused by water drink. The formula is exquisite and well-matched and is often modified and used by ancient and modern medical practitioners to treat various miscellaneous diseases of internal and external medicine，with significant therapeutic effects. In recent years，with the rapid development of modern pharmacology，research on the micro mechanism of CGG has been continuously developed and deepened，providing new ideas for the treatment of diseases with CGG. Therefore，the authors systematically searched databases such as China National Knowledge Infrastructure，Wanfang Data Knowledge Service Platform，VIP Database， and PubMed for literature on the clinical application and pharmacological mechanism of CGG published by Chinese and foreign scholars in recent years. This article summarized the literature from two aspects：the modern clinical application and mechanism of action of CGG and elaborated on the diseases treated by CGG in modern literature，involving digestive system，respiratory system，nervous system，endocrine system，circulatory system，urinary system，gynecology，as well as its application in reducing the side effects of radiotherapy and chemotherapy， gynecology， dermatology， ophthalmology， and orthopedics. At the same time，the mechanism of CGG in treating diseases may be related to anti-inflammatory，anti-oxidative stress， regulation of immunity， anti-fibrosis， anti-tumor， improvement of gastrointestinal flora and motility， protection of liver tissue， reduction of blood lipids and blood sugar， and regulation of hormone levels.

Objective To explore risk factors for cardiac valve calcification (CVC) in maintenance hemodialysis (MHD) patients and evaluate its impact on cardiovascular events and mortality. Methods Retrospective selection of 223 patients with MHD admitted to the Department of Nephrology of Jinshan Hospital, Fudan University from June 30, 2019 to June 30, 2024, and enrollment completed within one week of June 30, 2019. Patients were divided into CVC and non-CVC groups. Baseline data and 5-year follow-up data were collected. The binary logistic regression analysis was performed to explore the risk factors for CVC. Kaplan-Meier survival curve was used to analyze the survival rate of patients. Cox proportional hazard regression model was applied to evaluate the impact of CVC on the survival rates of MHD patients. Results Totally, 223 MHD patients with an average age of (58.4±13.5) years and an average dialysis duration of (64.0±55.4) months were involved. Among them, 136(61.0%) were males, 117(52.5%) were complicated with CVC. Age, dialysis duration, diabetic kidney disease (DKD), the serum corrected total calcium and phosphate, intact parathyroid hormone (iPTH), high-sensitive C-reactive protein (hsCRP), and homocysteine (Hcy) were independent related factors for CVC (P＜0.05). Both all-cause mortality (46.6% vs 28.7%) and cardiovascular mortality (33.3% vs 16.0%) were significantly higher in the CVC group than those in the non-CVC group (P＜0.01). Conclusions Age, dialysis duration, the primary disease, calcium and phosphate, and inflammation- and nutrition-related serum indicators are associated with CVC in MHD patients. CVC significantly increases mortality risk of MHD patients.

Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

Objective:It analyzed the population aggregation characteristics of the treatment costs for Traditional Chinese Medi-cine(TCM)dominant diseases,and make targeted recommendations for relevant health policies.Methods:A total of 205 medical insti-tutions were obtained through stratified whole-cluster sampling to analyze the composition of the beneficiary population based on Sys-tem of Health Accounts 2011 for the treatment costs of TCM dominant diseases for local residents in Beijing in 2019.Results:The treatment costs of Beijing's TCM dominant diseases are dominated by diseases that include basic western medicine treatment,with male patients'costs accounting for a higher proportion than those of females,and the trend of younger patients in types of diseases treated by TCM and the costs have mainly flowed to females,with more than 50%of the treatment costs being consumed by patients aged 60 years old and above.Conclusion:It is needed to pay attention to male and child patients aged 0～14 years and their priority diseases,strengthen the construction of Chinese medicine geriatric health services,and adopt differentiated strategies for different groups of people so as to maximize the advantages of Chinese medicine.

Objective To optimize the operational steps and processes in mouse cervical heterotopic heart transplantation by modifying the conventional cuff technique for vascular anastomosis and consequently establish a more stable cervical heterotopic heart transplantation model in mice.Methods C57BL/6 male mice (6～8 weeks old,weighing 20～24 g)were categorized into control (conventional cuff technique)and experimental groups (our"Anchoring Node"technique).Time for each surgical step,frequencies of vascular everting and vascular trimming,and the reasons for failure were recorded and compared between the 2 groups. Postoperative survival of heart allograft was determined by daily observation and touching,and the mice with the survival time>48 h were considered as successful model establishment.On the 7th and 14th days after surgery,HE staining was used to observe the pathologic changes in the vascular tissues at anastomosis.The expression of troponin T (cTnT)in the heart on the 7th day was detected with immunofluorescence assay. Results ① In the 25 hearts from each group,2 hearts from the experimental group and 8 from the control group failed,and the survival rate of heart allografts was 92％and 68％,respectively.In the experimental group,arterial and venous everting occurred at an average of 1 .16 times,with an average frequency of trimming of 0.04 times,while in the control group,arterial and venous everting was 2.00 and 2.28 times,respectively,with an average frequency of trimming of 0.21 and 0.46 times,respectively.② Significant differences were observed in the overall duration for cervical heterotopic heart transplantation (77.22±3.82 vs 87.49±8.01 min),vascular separation plus cannulation (30.06±2.68 vs 36.50±6.67 min),and cervical anastomosis (7.31±1 .08 vs 12.34±2.58 min)between the experimental and control groups (all P<0.05).③HE staining displayed that vascular patency was observed in the experimental group on the 7th and 14th days after surgery.④cTnT staining indicated no massive myocardial necrosis was seen in both groups. Conclusion Based on conventional cuff technique for mouse cervical heterotopic heart transplantation,our modified"Anchoring Node"technique ensures the stability and efficiency of one-man microscopic operation with controllable quality,with the advantages of longer postoperative survival of heart allograft,high patency rate of anastomotic vessels,good cardiac function,and fewer postoperative complications.

Objective:To investigate the treatment strategy for pediatric humeral supracondylar fractures with callus formation and displacement neglected for over 1 week.Methods:A retrospective analysis was made of the clinical data of 36 children who had been treated at Department of Pediatric Orthopaedics, Medical Center, The Second Affiliated Hospital, Inner Mongolia Medical University from January 2011 to January 2021 for humeral supracondylar fractures with callus formation and displacement neglected for over 1 week. There were 22 boys and 14 girls, with an age of (6.7±2.7) years (from 2.3 to 12.8 years). All fractures were Gartland type Ⅲ. The patients were divided into 2 groups according to their treatment methods: a closed reduction and percutaneous pinning (CRPP) group of 15 patients subjected to the CRPP treatment only, and a leverage group of 21 patients subjected to CRPP assisted by the "lever technique" with posterior elbow Kirschner wire prying and pulling. The 2 groups were compared in terms of operation time, fluoroscopy frequency, quality of reduction, and recovery time for elbow range of motion; the elbow range of motion, visual analogue scale (VAS), Mayo elbow performance score (MEPS) and complications were assessed at the last follow-up.Results:The 2 groups were comparable because there was no significant difference between them in the general information before operation ( P>0.05). All patients were followed up for (26.2±16.3) months (from 6 to 96 months). All the fractures obtained acceptable reduction and clinical union 4 to 6 weeks after operation. The operation time [(28.2±6.8) min] and fluoroscopy frequency [(27.0±6.0) times] in the leverage group were significantly less than those in the CRPP group [(40.8±10.8) min and (43.3±11.4) times] ( P<0.05). The CRPP group was significantly better than the leverage group in the intraoperative Baumann angle (78.1°±1.6° versus 73.7°±4.1°), lateral capitellohumeral angle (58.3°±2.6° versus 49.6°±5.2°) and horizontal rotation rate (109.5%±3.0% versus 103.2%±4.9%) ( P<0.05). The intraoperative reduction in the CRPP group was significantly closer to the normal mean value than that in the leverage group ( P<0.05). There was no significant difference in the recovery time for elbow range of motion between the CRPP and the leverage groups ( P>0.05). At the last follow-up, the Baumann angle (75.4°±2.8°) and the lateral capitellohumeral angle (53.2°±3.6°) in the leverage group were still significantly better than those in the CRPP group (78.3°±1.5° and 57.5°±2.3°) ( P<0.05). However, there was no significant difference in the elbow range of motion, VAS, MEPS or incidence of complications between the 2 groups ( P>0.05). Conclusion:To treat humeral supracondylar fractures with callus formation and displacement neglected for over 1 week in children, CRPP assisted by the "lever technique" with posterior elbow Kirschner wire prying and pulling is an efficient and accurate method, because it can lead to more satisfactory reduction than CRPP only.

Objective:To investigate the effect of ubiquitin binding enzyme 2T (UBE2T) on the radiosensitivity of lung adenocarcinoma and unravel its possible mechanism.Methods:A total of 45 patients pathologically diagnosed with different stages of lung adenocarcinoma and treated with radiotherapy in the Second Affiliated Hospital of Zunyi Medical University from March, 2019 to December, 2021 were enrolled, and the efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST1.1). All patients were divided into radiosensitive group ( n=25) and radioresistant group ( n=20). Radiosensitive group was complete remission (CR)+partial remission (PR), and radioresistant group was stable disease (SD) + progression disease (PD). Immunohistochemistry (IHC) was used to calculate the score based on the staining intensity and the number of positive cells. Chi-square test was combined to analyze the correlation between the expression level of UBE2T in paraffin specimens of lung adenocarcinoma patients and the radiosensitivity of patients. Lentivirus UBE2T-interfered (UBE2Tsh) A549 and UBE2T-overexpressed SPC-A-1 lung adenocarcinoma cells and their respective controls were constructed for irradiation and colony formation assay. The survivor fraction curve was fitted by single-hit multi-target model. The DNA double-strand break (DSB) marker γH2AX foci were detected by immunofluorescence (IF). The expression levels of UBE2T, γH 2AX and Rad51 proteins were detected by Western blot. Cell cycle and apoptosis rate of A549 were determined by flow cytometry. Binary variables were statistically analyzed by Fisher's exact probability method and measurement data were assessed by t-test. Results:High-expression level of UBE2T was correlated with the radiosensitivity of lung adenocarcinoma patients ( P<0.05). UBE2Tsh improved the radiosensitivity of A549 lung adenocarcinoma cells, and the sensitizing enhancement ratio (SER) was 1.795. UBE2T overexpression decreased the radiosensitivity of SPC-A-1 lung adenocarcinoma cells with an SER of 0.293. γH2AX foci number per cell were significantly increased in UBE2Tsh A549 cells after irradiation ( P<0.01) . Compared with the control group, the expression level of γH2AX protein was up-regulated ( P<0.01)and that of Rad51 protein was down-regulated in UBE2Tsh A549 cells after radiation ( P<0.001). Compared with the control group, the expression level of γH2AX protein was down-regulated ( P<0.05) and that of Rad51 protein was up-regulated in UBE2T overexpressed SPC-A-1 cells ( P<0.001). The proportion of UBE2Tsh A549 cells in G 2 phase was decreased ( P<0.01) and cell apoptosis was increased ( P<0.001). Conclusions:UBE2T might promote the radioresistance of lung adenocarcinoma cells by enhancing DNA DSB repair induced by radiotherapy, inducing cell cycle G 2 phase arrest, and reducing cell apoptosis.

Objective:To investigate the current status of psychosomatic medical service competence and training needs among general practice resident physicians.Methods:An online questionnaire survey was conducted from August to September 2021, among general practice resident physicians selected by cluster sampling from 4 affiliated hospitals of Tongji University. The questionnaire contained the basic information, the self-assessment and training needs of psychosomatic medical service competence of participants, and psychosomatic medical service requirements of patients in the community.Results:A total of 159 questionnaires were distributed, and 140 were collected (88.1%). The survey showed that 25.7% (36/140) of participants believed that 50% or more patients had physical symptoms accompanied by emotional problems; 29.3% (41/140) thought that 50% or more patients had sleep problems, but 60.0% (84/140) of them failed to provide appropriate treatment. The rate of "core knowledge and concepts of psychosomatic medicine" was 47.5% (665/1 400) and the correct rate of "common psychosomatic diseases" was (64.6±23.4)%. Merely 21.4% (30/140) participants reported satisfaction with the psychosomatic medical service competence; 62.8% (88/140) respondents believed that the coverage rate of the above-mentioned competence training in the current general practice residential training program was less than 50%, and 66.4% (93/140) supported that more psychosomatic training was "necessary". The acceptance rate of online training, workshops, MDT, and clinical practice ranged from 56.4% (79/140) to 63.4% (89/140).Conclusions:The survey indicates that there are large needs for psychosomatic medical services among patients in community, but the competence and confidence of general practice resident physicians to provide the service are significantly insufficient. Therefore, it is suggested to strengthen the training of psychosomatic medical service competence in the general practice residency training program.